The studies described in this proposal will allow comparison in aged mice (mice over 18 months old) and young adult mice of 1) influenza lung disease; 2) the prophylactic and therapeutic effects of the immune modulator, muramyl dipeptide (MDP), against influenza lung infection and against secondary bacterial pneumonias which often accompany this virus infection; and 3) virus-specific and non-specific immune responses in lungs of untreated and MDP-treated aged and young adult mice. Initial studies will be aimed at determining the optimal dose, schedule of inoculation and route of inoculation of MDP that will prevent or reduce influenza disease. These determinations are already underway in young mice and are expected to be completed prior to funding. In succeeding experiments, we will compare disease severity, efficacy of MDP, and assess the ability of alveolar macrophages and other lung leukocytes obtained from each test group of mice to phagocytize and kill Staphylococcus aureus, to produce interferon in vivo and in vitro, and to mediate virus-specific and non-specific cell mediated cytotoxicity in in vitro 51-chromium release assays. Each group will contain mice which will be observed for mortality over a 21-day period following virus challenge. Mice dying during this period will be assessed for influenza virus titers and for secondary bacterial infections. Correlations between local immune responses and the severity of lung disease which occurs in each test group will be made. These experiments will provide: insight into the relationships that exist between aging, immune responses and influenza virus disease severity, a mouse model to test different materials that may alter the susceptibilities of the aged to respiratory viruses and secondary bacterial infection, and finally determine the feasibility of using MDP or related immunologically active compounds in aged animals for treatment of respiratory illness.